The overall objective of this program is to develop a novel treatment for prostate cancer which exploits synergistic effects between radiation and IL-3 gene therapy. We have shown in previous studies that IL-3 sensitizes tumors to the effects of radiation and simultaneously induces systemic anti-tumor immunity capable of eliminating distant metastases. The proposed pre-clinical murine prostate tumor model studies have been designed to determine whether these local and systemic anti-tumor effects may be optimized by IL-3 tumor exposure before, during or after radiotherapy. We have chosen genetically modified allogeneic fibroblasts to deliver IL-3 to the tumor site. In our previous studies, equivalent anti-tumor effects were obtained with cytokine transduced tumor cells, syngeneic fibroblasts and allogeneic fibroblasts. For practical considerations, we will generate a master cell bank of a human allogeneic fibroblast cell line transfected with an IL-3 expression vector for subsequent use in clinical trials. Successful development of combined radiation and IL-3 gene therapy to enhance local radiation treatment and provide effective systemic therapy will have very significant implications for the treatment of prostate cancer. PROPOSED COMMERCIAL APPLICATION Approximately 50 percent of prostate cancer patients presumed to have curative localized disease will relapse with either local or metastatic tumors. The therapy to be developed in this program is designed to improve the efficacy of local radiotherapy and to stimulate anti-tumor immunity to treat metastatic disease. Successful development of this treatment will result in significant future clinical applications.